Vilazodone

Vilazodone is an Antidepressant agent in the Selective Serotonin Reuptake Inhibitor/5-HT_1A Receptor Partial Agonist class.

Vilazodone concentrations peaked at a median of 4-5 hours (Tmax) after Vilazodone administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food. Vilazodone AUC and Cmax in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness. Vilazodone is widely distributed and approximately 96-99% protein-bound. Administration of Vilazodone to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated. Vilazodone is mainly metabolized by cytochrome P450(CYP)3A4 and to a minor extent by CYP2C19 and CYP 2D6.1% of the dose is recovered unchanged in the urine and 2% of the dose is recovered unchanged in the feces.

Vilazodone shows side effects like Dry mouth, increased appetite, heartburn, gas, dizziness, pain, burning or tingling in the hands or feet, uncontrollable shaking of a part of the body, etc.

Vilazodone is available in the form of an Oral Tablet.

Vilazodone is available in India, Canada, the US, Mexico, Germany, China, Japan, Switzerland, and Spain.

Vilazodone belongs to the Selective Serotonin Reuptake Inhibitor/5-HT_1A Receptor Partial Agonist class and acts as an Antidepressant agent.

Vilazodone selectively inhibits serotonin reuptake in the central nervous system and acts as a partial agonist of the 5HT-1A receptor. The exact mechanism for how these effects translate to its antidepressant effects are not known though there is an association between these effects and antidepressive activity.

The Onset of action of Vilazodone is not clinically established.

The Time to peak plasma concentration of Vilazodone is approximately 4-5 hours.

Vilazodone is available in the form of an Oral Tablet.

Vilazodone tablet is taken orally, usually once daily.

Vilazodone is used to treat depression. Vilazodone is in a class of medications called serotonin modulators. It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Vilazodone is an Antidepressant agent belonging to the Selective Serotonin Reuptake Inhibitor/5-HT_1A Receptor Partial Agonist class.

Vilazodone enhances the serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown.

Vilazodone is approved for use in the following clinical indications

• Major depressive disorder, unipolar

Vilazodone is an antidepressant agent used to treat major depressive disorder that targets the 5-HT transporter and 5-HT1A receptors.

• Major depressive disorder, unipolar

Oral: Initial: 10 mg once daily for seven days, then increase to 20 mg once daily; may increase to 40 mg once daily after an additional ≥7 days based on response and tolerability (maximum dose: 40 mg/day).

Vilazodone is available in various strengths as 10 mg, 20 mg; 40 mg.

Vilazodone is available in the form of an Oral Tablet.

Vilazodone is contraindicated in patients with

• Monoamine Oxidase Inhibitors (MAOIs)

The use of MAOIs intended to treat psychiatric disorders with Vilazodone or within 14 days of stopping treatment with Vilazodone is contraindicated because of an increased risk of serotonin syndrome. The use of Vilazodone within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. Starting Vilazodone in a patient who is being treated with MAOIs or linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome.

• Suicidal thinking/behavior:

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients; consider risk before prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years of age. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with the health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Vilazodone is not approved for use in pediatric patients.

• Bleeding risk

May impair platelet aggregation, resulting in an increased risk of bleeding events, mainly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding (including GI bleeding) related to SSRI or SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

• Fractures

Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising.

• Ocular effects

May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients without an iridectomy for narrow-angle glaucoma risk factors.

• Serotonin syndrome

Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), mainly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors, including linezolid and intravenous methylene blue). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction

May cause or exacerbate sexual dysfunction.

• SIADH and hyponatremia

SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported (including severe cases with serum sodium <110 mmol/L), predominately in the elderly; reversible with treatment discontinuation. Volume depletion and/or concurrent use of diuretics likely increases risk.

• Mania/hypomania

May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer may be effective for acute treatment of bipolar major depressive episodes. Still, it should be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants. Patients presenting with depressive symptoms should be screened for bipolar disorder. Vilazodone is not FDA-approved for the treatment of bipolar depression.

• Seizure disorder

Use with caution in patients with a previous seizure disorder or condition predisposing to seizures, such as brain damage or alcoholism.

Consumption of alcohol is not recommended during the treatment with Vilazodone due to the increased risk of severe side effects such as dizziness, drowsiness, impaired judgment, impaired thinking, lethargy, restlessness, etc.

Vilazodone is excreted into the milk of lactating rats. The effect of Vilazodone on lactation and nursing in humans is unknown. Breast feeding in women treated with Vilazodone should be considered only if the potential benefit outweighs the potential risk to the child.

Vilazodone caused some developmental toxicity in rats but was not teratogenic in rats or rabbits. There are no adequate and well-controlled studies of Vilazodone in pregnant women. When treating pregnant women with Vilazodone, carefully consider whether the potential benefits outweigh the potential risks of treatment.

Common

Headache, Diarrhea, nausea, Palpitations, Dizziness, insomnia, drowsiness, fatigue, abnormal dreams, restlessness, paresthesia, delayed ejaculation, migraine, sedation, panic attack, ventricular premature contractions, Hyperhidrosis, night sweats, Decreased libido, weight gain, Xerostomia, abdominal pain, vomiting, dyspepsia, flatulence, increased appetite, abdominal distension, gastroenteritis, Erectile dysfunction, orgasm disturbance, Arthralgia, tremor, Blurred vision, xerophthalmia.

Rare

Acute pancreatitis, angle-closure glaucoma, cataract, hallucination, hyponatremia, irritability, mania, seizure, serotonin syndrome, skin rash, sleep paralysis, suicidal ideation, suicidal tendencies, urticaria.

Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed.

Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Opioid Agonists: May enhance the serotonergic effect of serotonin agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Selective Serotonin Reuptake Inhibitors: This may enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding.

Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Gilteritinib: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor.

The common side effects of Vilazodone include the following

Common side effects

Dry mouth, increased appetite, heartburn, gas, dizziness, pain, burning, or tingling in the hands or feet, uncontrollable shaking of a part of the body, unusual dreams, tiredness, joint pain, sexual problems in males; decreased sex drive, inability to get or keep an erection, or delayed or absent ejaculation, sexual problems in females; decreased sex drive, or delayed orgasm or unable to have an orgasm.

Rare side effects

Hives, swelling, difficulty breathing, loss of consciousness, seizures, fever, sweating, confusion, fast or irregular heartbeat, and severe muscle stiffness or twitching, agitation, hallucinations, loss of coordination, nausea, vomiting, or diarrhea, unusual bleeding or bruising, nosebleeds, small red or purple dots on the skin, hallucinations (seeing things or hearing voices that do not exist), headache, difficulty concentrating, memory problems, weakness, problems with coordination, increased falls, fainting.

• Pregnancy

Pregnancy Category C

Vilazodone caused some developmental toxicity in rats but was not teratogenic in rats or rabbits. There are no adequate and well-controlled studies of Vilazodone in pregnant women. When treating pregnant women with Vilazodone, carefully consider whether the potential benefits outweigh the potential risks of treatment.

• Nursing Mothers

Vilazodone is excreted into the milk of lactating rats. The effect of Vilazodone on lactation and nursing in humans is unknown. Breast feeding in women treated with Vilazodone should be considered only if the potential benefit outweighs the potential risk to the child.

• Pediatric Use

Clinical studies on the use of Vilazodone in pediatric patients have not been conducted; therefore, the safety and effectiveness of Vilazodone in the pediatric population have not been established. Vilazodone is not approved for use in pediatric patients.

• Geriatric Use

No dose adjustment is recommended based on age (see Figure 2). Results from a single-dose (20 mg) pharmacokinetic study in elderly (> 65 years-old) vs. young (24-55 years-old) subjects demonstrated that the pharmacokinetics were generally similar between the two age groups. Of the 2177 patients in clinical studies with Vilazodone, 37 (1.7%) were 65 years of age or older, and 272 (12.5%) were 55 to 64 years of age. Greater sensitivity of some older individuals cannot be ruled out. Serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event.

Four patients and 1 patient’s child experienced an overdose of Vilazodone; all recovered. The adverse reactions associated with overdose of Vilazodone at doses of 200-280 mg as observed in clinical trials included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation.

Management: No specific antidotes for vilazodone are known. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Gastric lavage with a large bore orogastric tube with appropriate airway protection, if needed, may be considered. Removal of vilazodone by dialysis has not been studied; however, the high volume of distribution of vilazodone suggests that dialysis will not be effective in reducing vilazodone plasma concentrations.

• Pharmacodynamic

Vilazodone increases serotonin levels in the brain by inhibiting the reuptake of serotonin while acting as a partial agonist on serotonin-1A receptors. Due to this activity vilazodone has sometimes been referred to as a selective partial agonist and reuptake inhibitor (SPARI).

• Pharmacokinetics

Absorption

Vilazodone concentrations peaked at a median of 4-5 hours (Tmax) after Vilazodone administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food. Vilazodone AUC and Cmax in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness.

Distribution

Vilazodone is widely distributed and approximately 96-99% protein bound. Administration of Vilazodone to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated.

Metabolism and Excretion

Vilazodone is mainly metabolized by cytochrome P450(CYP)3A4 and to a minor extent by CYP2C19 and CYP 2D6.1% of the dose is recovered unchanged in the urine and 2% of the dose is recovered unchanged in the feces.

• https://www.uptodate.com/contents/vilazodone-drug-information?search=vilazodone&source=panel_search_result&selectedTitle=1~21&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://go.drugbank.com/drugs/DB06684
• https://www.uptodate.com/contents/vilazodone-drug-information?search=vilazodone&source=panel_search_result&selectedTitle=1~21&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://medlineplus.gov/druginfo/meds/a611020.html
• https://www.drugs.com/dosage/vilazodone.html